Microtubule acetylation by ⍺TAT1 is essential for touch sensation in zebrafish but dispensable for embryonic development

Abstract Acetylation of α-tubulin at lysine 40 (α-tubK40Ac) is a conserved post-translational modification that occurs on the microtubule lumenal surface, but its developmental functions remain poorly defined. In zebrafish, morpholino knockdown of α-tubulin acetyltransferase 1 (αTAT1), the enzyme responsible for depositing α-tubK40Ac marks, has been reported to cause severe developmental defects, whereas genetic loss-of-function studies in mice found no overt role in development. Here, we generated αTAT1 loss-of-function alleles in zebrafish and found that, in contrast to morphants, mutants are viable, fertile, and develop normally. αTAT1 mutants lack detectable α-tubK40Ac in all examined tissues, indicating that no other enzyme compensates for loss of αTAT1. Both cilia and neurons normally display high levels of α-tubK40Ac and despite the complete loss of this modification in αTAT1 mutants, gross cilia structure and motility were preserved, and cilia-dependent developmental processes remained intact. However, αTAT1 mutants did exhibit defects in touch responsiveness, something which could be rescued by wild-type but not catalytically inactive αTAT1. These findings demonstrate that αTAT1 is solely responsible for α-tubK40Ac in zebrafish and that, while dispensable for embryonic development and ciliary function, this modification is required for normal somatosensory behavior. Competing Interest Statement The authors have declared no competing interest.